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https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#1
REVIEW
Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324619/identification-of-a-herv-k-env-surface-peptide-highly-recognized-in-ra-patients-a-cross-sectional-case-control-study
#2
G Mameli, G L Erre, E Caggiu, S Mura, D Cossu, Marco Bo, M L Cadoni, A Piras, N Mundula, E Colombo, G Buscetta, G Passiu, L A Sechi
Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19-37 , env-su 109-26 , env-su 164-186 , env-su 209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity...
March 21, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28324600/light-sheet-fluorescence-microscopy-chemical-clearing-and-labeling-protocols-for-ultramicroscopy
#3
Nina Jährling, Klaus Becker, Saiedeh Saghafi, Hans-Ulrich Dodt
Light-sheet microscopy is an effective technique in neuroscience, developmental biology, and cancer research for visualizing and analyzing cellular networks and whole organs in three dimensions. Because this technique requires specimens to be translucent they commonly have to be cleared before microscopy inspection. Here, we provide 3DISCO based protocols for preparing cleared samples of immuno-stained neural networks, lectin-labeled vascular networks, and Methoxy-X04 labeled beta-amyloid plaques in mice. 3DISCO utilizes the lipophilic solvents tetrahydrofuran (THF) and dibenzylether (DBE) for dehydration and successive clearing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324506/induction-of-site-specific-oxidative-damage-at-telomeres-by-killerred-fused-shelretin-proteins
#4
Rong Tan, Li Lan
Chronic oxidative stress is the major endogenous metabolic stress and contributes directly to telomere shortening and senescence. Understanding the dysfunction of telomeres under oxidative stress will greatly facilitate healthy aging and advance the treatment of aging-related diseases. Here, we describe the KR-TEL (KillerRed induced DNA damage at telomeres) system that induces site-specific oxidative damage at telomeres. We have developed the KR-TEL system by fusing killerred with the shelterin component TRF1 (KR-TRF1) or other shelterin proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324157/water-fat-mri-in-a-hibernator-reveals-seasonal-growth-of-white-and-brown-adipose-tissue-without-cold-exposure
#5
Amanda MacCannell, Kevin Sinclair, Lannette Friesen-Waldner, Charles A McKenzie, James F Staples
Obligate hibernators, such as ground squirrels, display circannual patterns which persist even under constant laboratory conditions, suggesting that they are regulated by endogenous rhythms. Brown adipose tissue (BAT) is important for thermogenesis during periodic arousals from hibernation when core body temperature rises spontaneously from 5 to 37 °C. In most small eutherians BAT growth requires several weeks of cold exposure. We hypothesized that in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), a hibernator, BAT growth is regulated, in part, by an endogenous rhythm and we predicted that this growth would precede the hibernation season without cold exposure...
March 21, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28324104/vasoprotective-activities-of-the-adrenomedullin-ramp2-system-in-endothelial-cells
#6
Xian Xian, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Megumu Tanaka, Teruhide Koyama, Hisaka Kawate, Lei Yang, Tian Liu, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after coronary intervention. We previously described the essential angiogenic function of the adrenomedullin (AM)-receptor activity-modifying protein 2 (RAMP2) system. In the present study, we assessed the vasoprotective actions of the endogenous AM-RAMP2 system using a wire-induced vascular injury model. We found that neointima formation and vascular smooth muscle cell proliferation were enhanced in RAMP2+/- male mice. The injured vessels from RAMP2+/- mice showed greater macrophage infiltration, inflammatory cytokine expression and oxidative stress than vessels from wild-type mice, and less re-endothelialization...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324063/dio2-thr92ala-reduces-deiodinase-2-activity-and-serum-t3-levels-in-thyroid-deficient-patients
#7
M G Castagna, M Dentice, S Cantara, R Ambrosio, F Maino, T Porcelli, C Marzocchi, C Garbi, F Pacini, D Salvatore
Context: A significant proportion of athyreotic LT4-treated patients experience hypothyroid-like symptoms. During LT4 replacement, levels of the active hormone triiodothyronine (T3) strictly depend on type-2-deiodinase (D2)-mediated activation of LT4. The Thr92Ala polymorphism and the 258 G/A in the DIO2 gene have been associated with various clinical conditions. Objectives: To investigate the effects of DIO2 polymorphisms in thyroid hormone homeostasis. Design: We compared the pre-surgical hormonal status of thyroidectomized LT4-treated patients who had a similar TSH level, to their post-surgery status, and analyzed their DIO2 genotype in a subgroup of 102/140 (72...
February 2, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324055/substrate-metabolism-and-insulin-sensitivity-during-fasting-in-obese-human-subjects-impact-of-gh-blockade
#8
Morten Høgild Pedersen, Mads Vandsted Svart, Janne Lebeck, Martin Bidlingmaier, Hans Stødkilde-Jørgensen, Steen Bønløkke Pedersen, Niels Møller, Niels Jessen, Jens O L Jørgensen
Context: Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. GH secretion increases during fasting and GH causes insulin resistance. Objective: To study the metabolic effects of GH blockade during fasting in obese subjects. Subjects and Methods: Nine obese males were studied thrice in a randomized design: 1) After an overnight fast (Control), 2) After 72 h fasting (Fasting) and 3) After 72 h fasting with GH blockade (pegvisomant) (Fasting + GHA)...
January 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#9
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324031/sex-steroid-hormones-and-fracture-in-a-multi-ethnic-cohort-of-women-the-women-s-health-initiative-study-whi
#10
Jane A Cauley, Michelle E Danielson, Guru Rajesh Jammy, Doug C Bauer, Rebecca Jackson, Jean Wactawski-Wende, Rowan T Chlebowski, Kristine E Ensrud, Robert Boudreau
CONTEXT: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. DESIGN AND SETTING: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study (WHI-OS). Incident non-spine fractures were identified in 381 Black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 White women who experienced an incident fracture was chosen...
January 25, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324024/thyroid-hormone-receptor-%C3%AE-controls-developmental-timing-and-regulates-the-rate-and-coordination-of-tissue-specific-metamorphosis-in-xenopus-tropicalis
#11
Luan Wen, Yuki Shibata, Dan Su, Liezhen Fu, Nga Luu, Yun-Bo Shi
Thyroid hormone (T3) receptor (TR) mediates the effects of T3 on organ metabolism and animal development. There are two TR genes, TRα and TRβ, in all vertebrates. During animal development, TRα expression is activated earlier than zygotic T3 synthesis and secretion into the plasma, implicating a developmental role of TRα both in the presence and absence of T3. Using T3-dependend amphibian metamorphosis as a model, we have previously proposed a dual functional model for TRs, in particular TRα, during development...
March 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#12
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324008/vessel-network-architecture-of-adult-human-islets-promotes-distinct-cell-cell-interactions-in-situ-and-is-altered-after-transplantation
#13
Christian M Cohrs, Chunguang Chen, Stephan R Jahn, Julia Stertmann, Helena Chmelova, Jürgen Weitz, Andrea Bähr, Nikolai Klymiuk, Anja Steffen, Barbara Ludwig, Virginia Kamvissi, Eckhard Wolf, Stefan R Bornstein, Michele Solimena, Stephan Speier
Islet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324005/insulin-inhibits-nrf2-gene-expression-via-heterogeneous-nuclear-ribonucleoprotein-f-k-in-diabetic-mice
#14
Anindya Ghosh, Shaaban Abdo, Shuiling Zhao, Chin-Han Wu, Yixuan Shi, Chao-Sheng Lo, Isabelle Chenier, Thierry Alquier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2-related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress and renal injury, inhibited renal Nrf2 and angiotensinogen (Agt) gene expression and up-regulated heterogeneous nuclear ribonucleoprotein F (hnRNP F) and hnRNP K expression in Akita mice with T1D...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323994/direct-regulation-of-histidine-ammonia-lyase-2-gene-by-thyroid-hormone-in-the-developing-adult-intestinal-stem-cells
#15
Nga Luu, Liezhen Fu, Kenta Fujimoto, Yun-Bo Shi
Most vertebrate organs utilize adult stem cells to maintain homeostasis and ensure proper repair when damaged. How such organ-specific stem cells are formed during vertebrate development is largely unexplored. We have been using the thyroid hormone (T3)-dependent amphibian metamorphosis to address this issue. Early studies in Xenopus laevis have shown that intestinal remodeling involves complete degeneration of the larval epithelium and de novo formation of adult stem cells through dedifferentiation of some larval epithelial cells...
February 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323953/activation-of-male-liver-chromatin-accessibility-and-stat5-dependent-gene-transcription-by-plasma-growth-hormone-pulses
#16
Jeannette Connerney, Dana Lau-Corona, Andy Rampersaud, David J Waxman
Sex-differences in pituitary growth hormone (GH) secretion (pulsatile in males vs near continuous/persistent in females) impart sex-dependent expression to hundreds of genes in adult mouse liver. STAT5, a GH-activated transcription factor that is essential for liver sexual dimorphism, is dynamically activated in direct response to each male plasma GH pulse. However, the impact of GH-induced STAT5 pulses on liver chromatin accessibility and downstream transcriptional events is unknown. Here, we investigate the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323936/the-steroid-metabolome-in-the-isolated-ovarian-follicle-and-its-response-to-androgen-exposure-and-antagonism
#17
Marie Lebbe, Angela E Taylor, Jenny A Visser, Jackson Kirkman-Brown, Teresa K Woodruff, Wiebke Arlt
The ovarian follicle is a major site of steroidogenesis, crucially required for normal ovarian function and female reproduction. Our understanding of androgen synthesis and metabolism in the developing follicle has been limited by sensitivity and specificity issues of previously used assays. Here we used liquid chromatography-tandem mass spectrometry to map the stage-dependent endogenous steroid metabolome in an encapsulated in vitro follicle growth system, from murine secondary through antral follicles. Furthermore, follicles were cultured in the presence of androgen precursors, non-aromatizable active androgen and androgen receptor (AR) antagonist to assess effects on steroidogenesis and follicle development...
February 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323934/menopausal-hormone-therapy-and-type-2-diabetes-prevention-evidence-mechanisms-and-clinical-implications
#18
Franck Mauvais-Jarvis, JoAnn E Manson, John C Stevenson, Vivian A Fonseca
Type 2 diabetes has reached epidemic proportions in the US. Large randomized controlled trials suggest that menopausal hormone therapy (MHT) delays the onset of type 2 diabetes in women. Still, the mechanisms and clinical implications of these associations are a matter of controversy. This review provides an up-to-date analysis and integration of epidemiological, clinical and basic studies, and proposes a mechanistic explanation for the effect of menopause and MHT on type 2 diabetes development and prevention...
March 8, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28323908/effects-of-protease-and-non-starch-polysaccharide-enzyme-on-performance-digestive-function-activity-and-gene-expression-of-endogenous-enzyme-of-broilers
#19
Lin Yuan, Mingfa Wang, Xiaotu Zhang, Zhixiang Wang
Three hundred one-day-old male broiler chickens (Ross-308) were fed corn-soybean basal diets containing non-starch polysaccharide (NSP) enzyme and different levels of acid protease from 1 to 42 days of age to investigate the effects of exogenous enzymes on growth performance, digestive function, activity of endogenous digestive enzymes in the pancreas and mRNA expression of pancreatic digestive enzymes. For days 1-42, compared to the control chickens, average daily feed intake (ADFI) and average daily gain (ADG) were significantly enhanced by the addition of NSP enzyme in combination with protease supplementation at 40 or 80 mg/kg (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/28323883/ubiquitously-expressed-human-beta-defensin-1-hbd1-forms-bacteria-entrapping-nets-in-a-redox-dependent-mode-of-action
#20
Judith Raschig, Daniela Mailänder-Sanchez, Anne Berscheid, Jürgen Berger, Adam A Strömstedt, Lioba F Courth, Nisar P Malek, Heike Brötz-Oesterhelt, Jan Wehkamp
Ever since the discovery of endogenous host defense antimicrobial peptides it has been discussed how these evolutionary conserved molecules avoid to induce resistance and to remain effective. An Human ß-defensin 1 (hBD1) is an ubiquitously expressed endogenous antimicrobial peptide that exhibits qualitatively distinct activities between its oxidized and reduced forms. Here, we explore these antimicrobial mechanisms. Surprisingly, using electron microscopy we detected a so far unknown net-like structure surrounding bacteria, which were treated with the reduced but not the oxidized form of hBD1...
March 21, 2017: PLoS Pathogens
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